Achievement and maintenance of sustained response during the Treatment for Adolescents With Depression Study continuation and maintenance therapy

Abstract

Context: The Treatment for Adolescents With Depression Study evaluated fluoxetine (FLX), cognitive behavioral therapy (CBT), and FLX/CBT combination (COMB) vs pill placebo in 439 adolescents with major depressive disorder. Treatment consisted of 3 stages: (1) acute (12 weeks), (2) continuation (6 weeks), and (3) maintenance (18 weeks).

Objective: To examine rates of achieving and maintaining sustained response during continuation and maintenance treatments.

Design: Randomized controlled trial. Response was determined by blinded independent evaluators.

Setting: Thirteen US sites.

Patients: Two hundred forty-two FLX, CBT, and COMB patients in their assigned treatment at the end of stage 1.

Interventions: Stage 2 treatment varied based on stage 1 response. Stage 3 consisted of 3 CBT and/or pharmacotherapy sessions and, if applicable, continued medication.

Main outcome measures: Sustained response was defined as 2 consecutive Clinical Global Impression-Improvement ratings of 1 or 2 ("full response"). Patients achieving sustained response were classified on subsequent nonresponse status.

Results: Among 95 patients (39.3%) who had not achieved sustained response by week 12 (29.1% COMB, 32.5% FLX, and 57.9% CBT), sustained response rates during stages 2 and 3 were 80.0% COMB, 61.5% FLX, and 77.3% CBT (difference not significant). Among the remaining 147 patients (60.7%) who achieved sustained response by week 12, CBT patients were more likely than FLX patients to maintain sustained response through week 36 (96.9% vs 74.1%; P = .007; 88.5% of COMB patients maintained sustained response through week 36). Total rates of sustained response by week 36 were 88.4% COMB, 82.5% FLX, and 75.0% CBT.

Conclusions: Most adolescents with depression who had not achieved sustained response during acute treatment did achieve that level of improvement during continuation and maintenance therapies. The possibility that CBT may help the subset of adolescents with depression who achieve early sustained response maintain their response warrants further investigation.

Trial registration: clinicaltrials.gov Identifier: NCT00006286.

Figure 1

Treatment for Adolescents with Depression Study (TADS): Flow diagram for the N = 242 who continued randomized treatment after 12 weeks of acute treatment. Reasons for discontinuation prior to randomization have been previously reported (TADS Team, 2004, JAMA, p. 811). COMB = combination of fluoxetine and cognitive behavior therapy; FLX = fluoxetine; CBT = cognitive behavior therapy; PBO = pll placebo; DC = discontinuation of randomized treatment due to premature termination, non-response at the end of Stage I, or study exit; OC (observed case) = youth still in randomized treatment arm; The 242 youths who started Stage II as an observed case were evaluated in the current analysis; N = Number of CGI-1 assessments completed for 242 cases at Week 18 and Week 36. All 112 patients assigned to the PBO condition discontinued randomized treatment at the end of Stage I as per protocol and are excluded from the current analysis.